1. Field of the Invention
This invention relates generally to diagnosis of a disease condition in a mammal. It is particularly directed to detecting lung cancer in a human by evaluating bioelectrical measurements taken between discreet points on the subject human body.
2. State of the Art
By definition, electrical impedance is the ratio of the voltage difference to the current across a circuit or a body (Ohm's law), and conductance is the inverse of impedance (1/impedance). The dielectric properties of human cells and tissue are widely recognized and are essential for several diagnostic procedures currently in use. The Coulter Counter for electronic cell counting, the electrocardiogram for assessing cardiac functioning, and the encephalogram for evaluating brain functioning are some common examples.
The dielectric properties of the human body are well-characterized in literature and provide the basis for several clinical tests including electrocardiography, electroencephalography, plethysmography, electrical conductance tomography and BIA. Moreover, there is clear evidence that cancerous tissues differ in their bioelectrical conductance properties compared to those of benign and adipose tissue, and a device using bioelectrical conductance measurements has been approved by the United States Food and Drug Agency for use as a diagnostic adjunctive to mammography in the work-up of breast cancer in women under 40 years of age. The same technology is currently being evaluated as a screening test. Investigations have also been conducted for various other malignancies including cervical, skin, lymph nodes, thyroid, and lung cancer. In the bioelectrical assessment of lung cancer, there is evidence that electrical impedance tomography is capable of imaging the lungs, however limited information exists concerning the most effective access points and the modalities for bioelectrical conductivity measurement.
Many clinical investigations have examined the potential of using electrical properties for aiding in cancer diagnosis. Aberg and colleagues reported on the use of electrical bio-conductance to assess skin cancers. They found separation of malignant melanoma and non-melanoma skin cancer from benign nevi with 75% and 87% specificity, respectively, and 100% sensitivity for both. This was considered equal to, or better than, conventional visual screening. Electrical conductance scanning also shows promise in lymph node evaluation in children and adults. Malich et al reported that of 106 sonographically suspicious lymph nodes in the head and neck region, electrical conductance scanning was able to detect 62 of 64 malignant nodes for a true positive rate of 96.9%. However in this study, only 19 of 42 inflammatory benign lymph nodes were correctly identified as benign for a true negative rate of 45.2%. The authors conclude that while these results are promising, further development work is needed to reduce the high number of false-positives. Similar results were reported when potentially malignant lymph nodes were evaluated in children using electrical conductance. Another recent prospective study of electrical conductance scanning of 64 patients who were undergoing surgery for possible thyroid malignancies found that it is a potentially useful imaging modality for differentiating thyroid neoplasms.
Breast cancer has probably been studied the most extensively with conductance technology. Investigations of electrical conductance scanning in patients with sonographically or mammographically suspicious lesions found that there were significant differences between the tissues of normal and abnormal subjects. By considering electrical conductance results in addition to ultrasound and mammography, the sensitivity of cancer detection increased from 86% to 95%. In 1999, the US FDA approved a multi-frequency conductance breast scanner (T-Scan 2000) for use as an adjunct to mammography for select patients. A recent study of the T-Scan 2000ED which used a modified algorithm provided preliminary evidence that electrical conductance scanning might be valuable for early detection of breast cancer in young women at increased risk for having disease at the time of scanning.
Other recent investigations have shown that conductance spectroscopy may be a viable screening tool for detection of cervical cancer. Additional studies in humans demonstrated altered electrical properties in tissues of patients with various cancers including lung, pancreas and colorectal compared to those without cancer. Several of these studies have been done in lung cancer patients providing evidence that alterations in bioelectrical conductance are evident in this patient population.
Although there is clear evidence that survival is increased by resection and oncolytic intervention of earlier stage lung cancer, detection at the earlier stages remains difficult. The current interest and ongoing investigation of using low-dose CT scanning for screening presents challenges as well. It is almost universally agreed that CT scanning of high risk subjects identifies nodules that qualify for further clinical evaluation, either by repeat CT scan or biopsy, and yet 92-96% of identified lesions will be found to be benign. As a result, the economic and health costs associated with using CT scan in this modality is not offset by clinical benefit.
Consequently, there is a long felt need for a non-significant risk, non-invasive technology that could be utilized in conjunction with CT scanning to further differentiate suspicious masses or nodules identified by CT. Such differentiating information desirably would be clinically meaningful in identifying which patients should proceed for further diagnostic evaluation and those that are likely to have a benign finding.